Animal-free regenerative biological solutions produced by 3D bioprinting

• Grant number: 21/12156-1
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Duration: April 01, 2022 - September 30, 2024
• Field of knowledge: Interdisciplinary Subjects
• Convênio/Acordo: SEBRAE-SP
• Principal Investigator: Janaina de Andrea Dernowsek
• Grantee: Janaina de Andrea Dernowsek
• Host Company: Bio.Inn Ltda
• CNAE: Fabricação de preparações farmacêuticas ; Pesquisa e desenvolvimento experimental em ciências físicas e naturais ; Atividades profissionais, científicas e técnicas não especificadas anteriormente
• City: São Paulo
• Pesquisadores principais: Jeniffer Farias dos Santos
• Associated researchers: Diego Rodney Rodrigues de Assis ; Williane Fernanda Siqueira
• Associated grant(s): 21/14955-9 - Animal-free regenerative biological solutions produced by 3D bioprinting, AP.PIPE
• Associated scholarship(s): 23/00258-0 - Mechanism of action of QMatrix on in vitro 3D artificial skin, BP.TT; 22/14682-5 - Bioink formulations and optimization for 3D tissue bioprinting, BP.TT; 22/09943-4 - Bioink formulations and optimization for 3D tissue bioprinting, BP.TT; 22/07910-1 - Crosslinking of collagen solution with a photochemical method for intradermal bioprinting, BP.TT; 22/04205-5 - QMatrix mechanism of action on in vitro 3D artificial skin, BP.TT

Abstract

Recent advances in additive manufacturing have enabled 3D printing of biocompatible materials, cells and supporting components in complex biological tissues. Nowadays, the 3D bioprinting process can be adapted to produce tissues in a variety of shapes and structural complexities, in addition to obtaining specific chemical, biomechanical and biological properties, aiming to create biomodels that mimic tissues close to real ones. This project aims to optimize the QuantumTissue technological platform patented in 2020. The platform is a process for obtaining extracellular matrix proteins (ECM) bioidentical to humans from bioprinted tissues with potential for future production in scale. A second objective is the development of potential innovative products such as a new generation of dermal fillers, joint fillers, collagen gel for R&D and other exploitable ones. The "QuantumTissue" platform has technological uniqueness, as it was created from the technology of bioprinting of human cells designed by the author of the project and produced in an innovative way. The steps of the bioprocess maintain the nobility of the proteins, maintaining the fibril structures of the original collagen (a process with no similar found in the search for prior art) and conducive to optimized crosslinking processes that allow for greater longevity in the organism in injectable and/or biofabricated tissues (figure 1). The result of the technological platform developed by the company is a high purity MEC protein solution with unique characteristics for applications in the food, cosmetic, pharmaceutical, dental and medical industries, and in a specific targeting the co-development with the pharmaceutical industry of a new generation of regenerative fillers, projected market at 10 billion dollars in 2026 and 8% growth per year. In an interview with more than 150 people from the industry and 20 medical specialists, the hypotheses that there is potential for obtaining, through the proposed process, a product with significant competitive advantages in relation to current alternatives for dermal and joint fillers were validated. The solution differs from alternatives based on hyaluronic acid by having fibrous collagen and other ECM proteins, providing greater durability for applications in view of its greater capacity for crosslinking and promoting the biostimulation of collagen in the native tissue itself. It differs from synthetic compounds/animal collagen/collagen alternatives for bringing less risk of adverse reaction, as we are proposing the use of organic compounds bioidentical to humans and a totally sterile process, free of reactive molecules (enzymes and other toxic molecules). As a design methodology, we will optimize the technological process that has six main stages: 2D cell culture and production of spheroids, formulation of hydrogels, preparation of biotint, bioprinting, homogenization and extraction of proteins, quality/safety analysis and crosslinking. The expected result is a refinement of the production process of biological solutions with unique properties such as high purity, fibrillar and improved crosslinking, making it attractive for industrial sectors. This work opens opportunities for biotechnological development of a new generation of regenerative fillers using what is most innovative in the field of biomanufacturing and would advance in the field of minimally invasive medicine. (AU)